Department of Histology and Embryology, Poznan University of Medical Sciences, Poland.
Doctoral School, Poznan University of Medical Sciences, Poland.
Adv Clin Exp Med. 2024 Apr;33(4):397-407. doi: 10.17219/acem/168603.
Adrenocortical carcinoma (ACC) affects approx. 2 in 1,000,000 individuals in the USA, and is more common in females than males. Adrenocortical carcinoma often presents with severe symptoms, such as abdominal pain, high blood pressure, acne, hair overgrowth, and voice deepening.
Research on ACC constitutes a large body of published data. There is an increased need for easy access to ACC-derived biological material. Moreover, there are limited numbers of human cell lines available. For this reason, we attempted to differentiate human induced pluripotent stem cells (hiPSCs) into adrenocortical-like cells to establish a new functional cell line.
We conducted a long-term differentiation process (35 and 70 days) in the presence of growth factors (GFs), forskolin and conditioned medium collected from the human adrenal carcinoma (HAC15) cell line. Then, we analyzed the gene expression profile of the differentiated cells.
The obtained cells possess features characteristic of all 3 primary germ layers. Interestingly, the differentiated cells demonstrated an extremely high level of gene expression for those involved in endocrine processes, namely glycoprotein hormones, alpha polypeptide (CGA), insulin receptor substrate 4 (IRS4), and pancreatic progenitor cell differentiation and proliferation factor-like protein (PPDPFL).
The results of the study indicate that we obtained progenitors derived from endoderm with some characteristics of pancreatic-like cells. The endodermal derivative differentiation is a very challenging and complicated process; thus, the results presented in this study deserve closer consideration.
在美国,约每 100 万人中就有 2 人会患上肾上腺皮质癌(ACC),且女性比男性更为常见。肾上腺皮质癌常伴有严重症状,如腹痛、高血压、痤疮、毛发过度生长和声音变深。
针对 ACC 的研究已经产生了大量已发表的数据。人们对 ACC 衍生的生物材料的获取需求日益增加。此外,可用的人源细胞系数量有限。基于此,我们试图将人诱导多能干细胞(hiPSC)分化为肾上腺皮质样细胞,以建立新的功能性细胞系。
我们使用生长因子(GFs)、forskolin 和人肾上腺皮质癌细胞系(HAC15)收集的条件培养基进行了长期分化过程(35 天和 70 天)。然后,我们分析了分化细胞的基因表达谱。
获得的细胞具有所有 3 个初级胚层的特征。有趣的是,分化细胞表现出参与内分泌过程的基因表达水平极高,即糖蛋白激素、α 多肽(CGA)、胰岛素受体底物 4(IRS4)和胰腺祖细胞分化和增殖因子样蛋白(PPDPFL)。
研究结果表明,我们获得了具有某些胰腺样细胞特征的内胚层衍生祖细胞。内胚层衍生物的分化是一个非常具有挑战性和复杂的过程;因此,本研究的结果值得进一步关注。